Objectives: To determine the prevalence and associated factors of work-related depression among the employees of a shoe manufacturing factory in Haiphong City, Vietnam. Material and Methods: We carried out this cross-sectional study among 420 workers in 2012 in Le Lai II Shoe Manufacturing Factory in Haiphong City, Vietnam using Karasek’s Job Content Questionnaire (JCQ) and the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) tool for measuring depression. Results: The study results show that a relatively high proportion of workers (20.7%) belongs to the high-strain group based on Karasek’s model. The prevalence of work-related depression among workers was relatively high (18.8%). The factors associated with depression at work were high psychological demand (adjusted OR = 3.0, 95% CI: 1.1–8.3), low social support (adjusted OR = 4.7, 95% CI: 1.2–12.8), inadequate work protection materials (OR = 4.1, 95% CI: 2.2–10.1) and work absenteeism (OR = 6.2, 95% CI: 2.5–18.9). Conclusions: Strengthening the social support network (involving supervisors and co‑workers), reducing psychological job demand and assuring work protection materials at the workplace may highly facilitate reducing work-related depression.